Budgetary impact analysis of buprenorphinenaloxone combination (Suboxone®) in Spain

Background: Opioid addiction is a worldwide problem. Agonist opioid treatment (AOT) is the most widespread and frequent pharmacotherapeutic approach. Methadone has been the most widely used AOT, but buprenorphine, a partial kappa-opiod agonist and a my-opiod antagonist, is fast gaining acceptance. The objective was to assess the budgetary impact in Spain of the introduction of buprenorphine-naloxone (B/N) combination. Methods: A budgetary impact model was developed to estimate healthcare costs of the addition of B/N combination to the therapeutic arsenal for treating opioid dependent patients, during a 3-year period under the National Health System perspective. Inputs for the model were obtained from the specialized scientific literature. Detailed information concerning resource consumption (drug cost, logistics, dispensing, medical, psychiatry and pharmacy supervision, counselling and laboratory test) was obtained from a local expert panel. Costs are expressed in euros ( , 2010). Results: The number of patients estimated to be prescribed B/N combination was 2,334; 2,993 and 3,589 in the first, second and third year respectively. Total budget is 85,766,129; 79,855,471 and 79,137,502 in the first, second and third year for the scenario without B/N combination. With B/N combination the total budget would be 86,589,210; 80,398,259 and 79,708,964 in the first, second and third year of the analyses. Incremental cost/ patient comparing the addition of the B/N combination to the scenario only with methadone is 10.58; 6.98 and 7.34 in the first, second and third year respectively. Conclusion: Addition of B/N combination would imply a maximum incremental yearly cost of 10.58 per patient compared to scenario only with methadone and would provide additional benefits

Consumo de jamón curado e incidencia de eventos cardiovasculares, hipertensión arterial o ganancia de peso

Fundamento y objetivo: El jamón curado es uno de los alimentos característicos de la dieta mediterránea española. Sin embargo, no existe ningún estudio epidemiológico prospectivo que haya valorado sus efectos sobre la salud humana. Nuestro objetivo fue evaluar la asociación entre el consumo de jamón curado y la incidencia de hipertensión arterial, enfermedad cardiovascular y/o ganancia de peso. Sujetos y método: En una cohorte epidemiológica prospectiva y dinámica de 13.293 graduados universitarios (Proyecto SUN) se analizó la incidencia de enfermedad cardiovascular, hipertensión arterial y la ganancia de peso a lo largo de un seguimiento máximo de 6 años. Se ajustaron modelos de regresión de Cox para estimar hazard ratios (riesgos relativos [RR]) tras ajustar por posibles factores de confusión. Resultados: El consumo de jamón en los niveles más altos (> 4 raciones/semana) no presentaba asociación con la incidencia de eventos cardiovasculares (RR=1,02; [IC 95%: 0,44-2,39]), tras ajustar por edad, sexo, ingesta energética total y patrón dietético, en comparación con los consumos inferiores a una vez por semana. Al repetir esta comparación para la hipertensión, y tras ajustar por edad, sexo, ingesta energética total e índice de masa corporal, se encontró un RR = 0.74 (IC 95%: 0.55-1.01). En la comparación del cambio de peso medio anual entre estas mismas categorías extremas de consumo (=4 raciones) se encontró una diferencia no significativa de 0,033 kg (IC 95%: -0,041 a +0,107) en la ganancia media de peso al año tras ajustar por sexo, edad, tabaco, actividad física e índice de masa corporal inicial. Conclusiones: Los resultados de esta cohorte no proporcionan evidencia de que el consumo de jamón curado se asocie a mayor riesgo cardiovascular, de hipertensión arterial o de ganancia de peso.Background and objective: Cured ham is a characteristic food in Spanish Mediterranean diet. However, no prospective epidemiologic study assessing its effects on human health is available. Our aim was to assess the association between the consumption of cured ham and cardiovascular disease, hypertension or weight gain. Subjects and Method: In a prospective and dynamic epidemiologic cohort composed exclusively of university graduates (the SUN Project, n=13,293), we analyzed the incidence of cardiovascular disease, hypertension or average yearly weight gain after a maximum follow-up of 6 years. Cox (proportional hazards) regression models were fitted to estimate hazard ratios (relative risks [RR]) after adjusting for potential confounding. Results: No association was found between higher levels of consumption of cured ham (> 4 servings/week) and the incidence of cardiovascular disease (RR=1.02; [95%CI]: 0.44-2.39), in analyses adjusted for age, sex, total energy intake and dietary pattern, compared to the consumption of less than one serving a week. When we repeated this comparison for the incidence of hypertension, and adjusting for age, sex, total energy intake and body mass index, the RR was 0.74 (95% CI: 0.55-1.01). In the comparison of average yearly weight gain between these extreme categories of cured ham consumption (=4 servings/week) a non-significant difference of 0.033 kg (95% CI: -0.041 to 0.107) was found after adjusting for sex, age, smoking, physical activity, and baseline body mass index. Conclusions: The results of this cohort study do not support any association between the consumption of cured ham and a higher risk of cardiovascular disease, hypertension or weight gain

Correction: Martínez-González, M.A. et al. Transferability of the Mediterranean Diet to Non-Mediterranean Countries. What Is and What Is Not the Mediterranean Diet. Nutrients 2017, 9, 1226

The authors have requested that the following changes be made to their paper [1]

Dietary patterns and total mortality in a Mediterranean cohort: the SUN project

BACKGROUND: Different dietary patterns have been associated with several health outcomes, including morbidity and mortality. There is little evidence on the association between empirically derived dietary patterns and all-cause mortality in Southern European populations. OBJECTIVE: The aim of our study was to prospectively evaluate the association between an empirically derived dietary pattern and all-cause mortality. DESIGN: The Seguimiento Universidad de Navarra (SUN) Project is an ongoing, multipurpose, prospective and dynamic Spanish cohort. PARTICIPANTS/SETTING: Participants were a prospective cohort of 16,008 middle-aged Spanish adults. All of them were university graduates (alumni) (59.6% women, mean age 38 years). Usual diet was assessed at baseline with a validated semiquantitative food frequency questionnaire. MAIN OUTCOME MEASURES: Deaths were confirmed by review of medical records and of the National Death Index. STATISTICAL ANALYSIS: Dietary patterns were ascertained through a factor (principal component) analysis based on 30 predefined food groups. Participants were classified according to tertiles of adherence to the three main dietary patterns identified with factor analysis. Cox regression models were fitted to estimate multivariable-adjusted hazard ratios and 95% CIs for mortality. RESULTS: Three major dietary patterns were identified. They were labelled Western dietary pattern (rich in red and processed meat, potatoes, and fast food), Mediterranean dietary pattern (rich in vegetables, fish and seafood, fruits, and olive oil), and alcoholic beverages dietary pattern. During follow-up, 148 deaths were reported (mean age at death 54.5 years). After adjustment for potential confounders, the lowest risk of all-cause mortality was found in the tertile of highest adherence to the Mediterranean dietary pattern (adjusted hazard ratio for third vs first tertile 0.53, 95% CI 0.34 to 0.84) (P for trend <0.01). The Western dietary pattern and alcoholic beverages dietary pattern showed no significant association with mortality. CONCLUSIONS: Greater adherence to an empirically derived dietary pattern approaching the traditional Mediterranean diet was associated with a reduction in the risk of all-cause mortality among middle-aged Mediterranean adults

Associations between overall, healthful, and unhealthful low-fat dietary patterns and breast cancer risk in a Mediterranean cohort: The SUN project

Objectives: Dietary patterns may have a greater influence on human health than individual foods or nutrients, and they are also of substantial interest in the field of breast cancer prevention. Beyond the adequate balance of macronutrients, evidence indicates that the quality of macronutrient sources may play an important role in health outcomes. We sought to examine the relationship between healthful and unhealthful low-fat dietary patterns in relation to breast cancer. Methods: We used observational data from a Mediterranean cohort study (the Seguimiento Universidad de Navarra project). We prospectively followed 10 930 middle-aged women initially free of breast cancer during a median follow-up of 12.1 y. We calculated an overall, an unhealthful, and a healthful low-fat diet score, based on a previously validated 136-item food frequency questionnaire and grouped participants into ter- tiles. Incident breast cancer—overall and stratified by menopausal status—was the primary outcome. It was self-reported by participants and confirmed based on medical reports or consultation of the National Death Index. We used multivariable Cox regression models adjusted for potential confounders. Results: During 123 297 person-years of follow-up, 150 cases of incident breast cancer were confirmed. No signifi- cant associations were observed for overall or premenopausal breast cancer. For postmenopausal women, we observed a significant association for moderate adherence to the unhealthful low-fat dietary score and postmeno- pausal breast cancer (comparing tertile 2 to tertile 1; hazard ratio = 2.18; 95% confidence interval, 1.15 4.13). Conclusions: In conclusion, no clear associations were observed, although more research is needed to address the association between an unhealthful dietary pattern and postmenopausal breast cancer risk

Egg consumption and dyslipidemia in a Mediterranean cohort

Introduction and objectives: Our aim was to prospectively evaluate the association between egg consumption and dyslipidemia in a Mediterranean cohort. Methods: We followed-up 13,104 Spanish university graduates for a mean period of 8 years. Dietary habits at baseline were assessed using a validated semi-quantitative 136-item food-frequency questionnaire. Self-reported blood concentrations of total cholesterol, high-density lipoproteins cholesterol (HDL-c) and triglycerides were evaluated according to categories of egg consumption after 6 and 8 years of follow-up. We also assessed the association between baseline egg consumption and the incidence of hypercholesterolemia, low HDL-c concentrations and hypertriglyceridemia during follow-up. Results: We observed a significant inverse association for intermediate levels of egg consumption (2 to 4 eggs/week vs. less than 1 egg/week) and hypertriglyceridemia with OR = 0.71 (95% confidence interval [CI]: 0.54 to 0.93, p < 0.05) in the multivariable-adjusted model. Using HDL-c values after 8-year follow-up, we found an association between higher egg consumption and lower HDL-c levels (p for trend = 0.02) with an adjusted difference of –4.01 mg/dl (-7.42 to -0.61) for > 4 vs. < 1 egg/week. Lower means of triglycerides were found in each of the three upper categories of egg consumption compared to the lowest category (< 1 egg/week) with significant results for some of these categories both after 6 and 8 year follow-up. Conclusions: Our data do not support that higher egg consumption was associated with abnormal blood levels of total cholesterol or triglycerides; an inverse association with HDL-c as a quantitative variable was found only in one of our analyses.Introducción y objetivos: evaluar prospectivamente la asociación entre el consumo de huevo y el riesgo de dislipidemia en una cohorte mediterránea. Métodos: se siguieron 13.104 graduados universitarios españoles durante un periodo medio de 8 años. La dieta se evaluó al inicio utilizando un cuestionario semicuantitativo de frecuencia de consumo de alimentos repetidamente validado. Las concentraciones sanguíneas de colesterol total, lipoproteínas de alta densidad (HDL-c) y triglicéridos autorreferidas fueron evaluadas según categorías de consumo de huevo tras 6 y 8 años de seguimiento. También se evaluó la asociación entre el consumo basal de huevo y la incidencia de hipercolesterolemia, concentraciones bajas de HDL-c e hipertrigliceridemia durante el seguimiento. Resultados: se observó una asociación entre los niveles intermedios de consumo de huevo (2-4 unidades/semana frente a < 1 unidad/semana) y menor riesgo de hipertrigliceridemia con OR = 0,71 (intervalo de confianza del 95% [IC]: 0,54 a 0,93, p < 0,05) en el modelo más ajustado. Tras 8 años de seguimiento, encontramos una asociación entre un mayor consumo de huevo y menores niveles de HDL-c (p tendencia lineal = 0,02) con una diferencia ajustada de -4,01 mg/dl (-7,42 a -0,61) para > 4 vs. < 1 unidad/semana. Se encontraron menores concentraciones de triglicéridos en las tres categorías superiores de consumo de huevo en comparación con la inferior con resultados significativos para algunas de estas categorías después de 6 y 8 años de seguimiento. Conclusiones: un mayor consumo de huevo no se asoció con niveles anormales de colesterol total o triglicéridos; se encontró una asociación inversa con HDL-c como variable cuantitativa solo en uno de nuestros análisis

Validation of the English version of the 14-Item Mediterranean diet adherence screener of the PREDIMED study, in people at high cardiovascular risk in the UK

The aim of this study was to examine the validity of the English version of the PREvencion con DIetaMEDiterranea (PREDIMED) 14-item Mediterranean Diet Adherence Screener (MEDAS), a brief questionnaire assessing adherence to the Mediterranean diet (MedDiet), which was used in the PREDIMED trial for assessment and immediate feedback. This instrument (MEDAS) was administered to 96 adults with a high cardiovascular risk (66% women, mean age 68.3 ± 6.0 years), recruited from general practices in Bristol, UK. Participants then completed a 3-day estimated food record, and the MEDAS was administered again one month later. A MedDiet score (range = 0-14) was calculated from the MEDAS' administrations and food record to assess concurrent validity and test-retest reliability. Predictive validity was assessed by examining the association of the MEDAS-derived score with cardiometabolic risk factors and dietary intakes derived from the food records. The MEDAS-derived MedDiet score was higher by 1.47 points compared to food records (5.47 vs.4.00, p < 0.001), correlated moderately with the record-derived score (r = 0.50, p < 0.001; ICC = 0.53, p < 0.001) and there was borderline fair agreement between the two methods (¿ = 0.19, 95% CI 0.07-0.31, p = 0.002; 95% limits of agreement -2.2, 5.1). Exact agreement within score categories and gross misclassificationwere 45.8% and 21.9%, respectively. The distribution of dietary intakes, reported on the food records by the MEDAS-derived total MedDiet score, was in the expected direction, but no association was observed with cardiometabolic risk factors. The two administrations of the MEDAS produced similar mean total MedDiet scores (5.5 vs. 5.4, p = 0.706), which were correlated (r and ICC = 0.69, p < 0.001) and agreed fairly (¿ = 0.38, 95% CI 0.24-0.52, p < 0.001; 95% limits of agreement -3.1, 3.2). The English version of the MEDAS has acceptable accuracy and reliability for assessing MedDiet adherence among individuals with a high cardiovascular risk, in the UK, and can be used to rank individuals according to MedDiet adherence in research and practice

Validity and reproducibility of a semi-quantitative food frequency questionnaire in Spanish preschoolers - The SENDO project

Introduction: nowadays, it is important to determine whether food frequency questionnaires (FFQ) are valid tools to collect information on usual diet in children. Objective: we evaluated the reproducibility and validity of the semi-quantitative FFQ used in a Spanish cohort of children aged 4-7 years. Methods: to explore its reproducibility, parents filled a 138-item FFQ at baseline (FFQ-0) and then one year later (FFQ-1). To explore its validity, the FFQ-1 was compared with four weighed 3-day dietary records (DRs) that were used as standard of reference. To estimate associations we calculated deattenuated Pearson’s correlation coefficients to correct for season-to-season variability, and the Bland-Altman index. We also calculated the weighted kappa index and assessed participant’s gross misclassification across quintiles. We analyzed data from 67 (for reproducibility) and 37 (for validity) children aged 4-7 years old, recruited by the pilot study of the SENDO project. Results: regarding reproducibility, we found mean Bland-Altman indexes of 0-10.45 % for nutrients and 1.49 %-10.45 % for foods. The adjusted r ranged between 0.29 and 0.71, and between 0.27 and 0.74 for nutrients and foods, respectively. Regarding validity, we found mean Bland-Altman indexes of 0 %-16.22 % and 0 %-10.81 % for nutrients and for food groups, respectively. The deattenuated r ranged between 0.38 and 0.81 for nutrients, and between 0.53 and 0.68 for foods. The weighted kappa index for agreement across quintiles ranged from 54.1 to 85.1 for nutrients, and from 55.4 to 78.4 for food groups. Conclusions: our results showed acceptable levels of both reproducibility and validity, and that the ad-hoc developed FFQ is a valid tool for assessing usual diet in Spanish preschoolers.Introducción: es importante determinar si los cuestionarios de frecuencia de consumo de alimentos (CFCA) son herramientas válidas para recopilar información sobre la dieta habitual en los niños. Objetivo: evaluar la reproducibilidad y validez del CFCA semi-cuantitativo de una cohorte española de niños de 4 a 7 años. Métodos: en total se estudiaron 67 (para reproducibilidad) y 37 (para validez) niños de 4 a 7 años de edad del estudio piloto del proyecto SENDO. Para explorar la reproducibilidad, los padres cumplimentaron el CFCA basalmente (CFCA-0) y al año (CFCA-1). Para explorar la validez, el CFCA-1 se comparó con cuatro registros dietéticos (DR) pesados de 3 días. Calculamos coeficientes de correlación de Pearson desatenuados para corregir la variabilidad inter-estacional, y el índice de Bland-Altman. El índice kappa ponderado permitió evaluar la clasificación errónea de los participantes entre quintiles. Resultados: respecto a la reproducibilidad, encontramos índices promedio de Bland-Altman de 0-10,45 % para los nutrientes y de 1,49-10,45 % para los alimentos. La r ajustada varió entre 0,29 y 0,71, y entre 0,27 y 0,74 para nutrientes y alimentos, respectivamente. En cuanto a la validez, encontramos índices promedio de Bland-Altman de 0-16,22 % y 0-10,81 % para nutrientes y alimentos, respectivamente. La r desatenuada osciló entre 0,38 y 0,81 para los nutrientes y entre 0,53 y 0,68 para los alimentos. El índice kappa ponderado para el acuerdo entre quintiles varió entre 54,1 y 85,1 para los nutrientes y entre 55,4 y 78,4 para los grupos de alimentos. Conclusiones: nuestros resultados mostraron niveles aceptables tanto de reproducibilidad como de validez. El FFQ desarrollado ad hoc es una herramienta válida para evaluar nutrientes y alimentos en preescolares españoles

Repeatability of food frequency assessment tools in relation to the number of items and response categories included

Background: Accuracy of a measurement is a cornerstone in research in order to make robust conclusions about the research hypothesis. Objective: To examine whether the number of items (questions) and the number of responses of consumption included in nutritional assessment tools influence their repeatability. Methods: During 2009, 400 participants (250 from Greece, 37±13 yrs, 34% males and 150 participants from Spain, 39±17 yrs, 41% males) completed a diet index with 11-items and binary (yes/no) responses, a diet-index with 11-items and 6-scale responses, a 36-item and a 76-item food frequency questionnaire (FFQ) with 6-scale responses. Participants completed these tools, twice, within 15-days period. Spearman-Brown (rsb), Kendall’s tau coefficients and the Bland-Altman method were applied to answer the research hypothesis. Results: The highest repeatability coefficient was observed for the 11-items with binary responses index (rsb=0.948, p<0.001), followed by the 11-items with 6-scale responses index (rsb=0.943, p<0.001), the 36-item (rsb=0.936, p<0.001) and the 76-item FFQs (rsb=0.878, p<0.001). Statistical comparisons revealed no significant differences between repeatability coefficients of the first three tools (p>0.23); whereas the aforementioned tools had significantly higher repeatability coefficients as compared with the 76-item FFQ (p=0.002). Sub-group analyses by gender, education, smoking and clinical status, confirmed the aforementioned results. Conclusion: Repeatability has been revealed for all food frequency assessment tools used, irrespective of the number of items or the number of responses included

Human CD127 negative ILC2s show immunological memory

ILC2s are key players in type 2 immunity and contribute to maintaining homeostasis. ILC2s are also implicated in the development of type 2 inflammation–mediated chronic disorders like asthma. While memory ILC2s have been identified in mouse, it is unknown whether human ILC2s can acquire immunological memory. Here, we demonstrate the persistence of CD45RO, a marker previously linked to inflammatory ILC2s, in resting ILC2s that have undergone prior activation. A high proportion of these cells concurrently reduce the expression of the canonical ILC marker CD127 in a tissue-specific manner. Upon isolation and in vitro stimulation of CD127−CD45RO+ ILC2s, we observed an augmented ability to proliferate and produce cytokines. CD127−CD45RO+ ILC2s are found in both healthy and inflamed tissues and display a gene signature of cell activation. Similarly, mouse memory ILC2s show reduced expression of CD127. Our findings suggest that human ILC2s can acquire innate immune memory and warrant a revision of the current strategies to identify human ILC2s.</p